Pharmaceutically active drugs can exist in different solid forms. For example, a drug may exist in different crystalline forms which have different physical, physic-chemical and chemical properties.
Different physical or physic-chemical properties can cause different crystalline forms of the same drug to have largely different processing and storage performance. Such physical or physico-chemical properties include, for example, thermodynamic stability, crystal morphology [form, shape, structure, particle size, particle size distribution, color, degree of crystallinity, ripple behavior, flowability, density, bulk density, powder density, apparent density, vibrated density, depletability, emptyability, hardness, deformability, grindability, compressability, compactability, brittleness, elasticity, caloric properties [particularly melting point], solubility [particularly equilibrium solubility, pH dependence of solubility], dissolution [particularly dissolution rate, intrinsic dissolution rate], reconstitutability, hygroscopicity, tackiness, adhesiveness, tendency to electrostatic charging, and the like.
In addition, different chemical properties can cause different crystalline forms of the same drug to have largely different performance properties. For example, a crystalline form having a low hygroscopicity (relative to other crystalline forms) can have superior chemical stability and longer shelf-life stability (cf. R. Hilfiker, Polymorphism, 2006 Wiley VCH, pp 235-242 and 251-252).
In medicine, the treatment of pain is of great importance and although a significant number of drugs are known for and established in the treatment of pain, there remains, for instance with regard to drug-related side-effects, a demand for improved pain medication, especially for the treatment of strong/severe and/or chronic and/or neuropathic pain. Consequently, a great deal of effort is still being invested by pharmaceutical companies into the development of new, improved analgesics.
One particular drug that is of great interest especially for the use in treating pain, especially chronic and/or neuropathic pain is cis-(E)-4-(3-Fluorophenyl)-2′,3′,4′,9′-tetrahydro-N,N-dimethyl-2′-(1-oxo-3-phenyl-2-propenyl)-spiro[cyclohexane-1,1′[1H]-pyrido[3,4-b]indol]-4-amine, which is described in WO2012013343-A1. The chemical structure of this drug is depicted below as the compound of formula (I):

The solid forms of cis-(E)-4-(3-Fluorophenyl)-2′,3′,4′,9′-tetrahydro-N,N-dimethyl-2′-(1-oxo-3-phenyl-2-propenyl)-spiro[cyclohexane-1,1′[1H]-pyrido[3,4-b]indol]-4-amine that are known so far are not satisfactory in every respect and consequently there is a demand for advantageous solid forms, especially crystalline forms. Especially, there is a demand for solid forms of cis-(E)-4-(3-Fluorophenyl)-2′,3′,4′,9′-tetrahydro-N,N-dimethyl-2′-(1-oxo-3-phenyl-2-propenyl)-spiro[cyclohexane-1,1′[1H]-pyrido[3,4-b]indol]-4-amine that have advantageous properties for the use of this compound in pharmaceutical compositions and for use in methods of preparing such pharmaceutical compositions.
This object has been achieved by the present invention. It has surprisingly been found that different crystalline forms of cis-(E)-4-(3-Fluorophenyl)-2′,3′,4′,9′-tetrahydro-N,N-dimethyl-2′-(1-oxo-3-phenyl-2-propenyl)-spiro[cyclohexane-1,1′[1H]-pyrido[3,4-b]indol]-4-amine can be prepared which have advantageous properties, especially for the use in pharmaceutical compositions. These inventive crystalline forms are described herein.